Unravelling the role of novel uncharacterised long non-coding RNAs in the control of cell fate


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Katerina Bountali1,Mirna Mourtada-Maarabouni1
1Keele University

Abstract

Background

The advances in Next Generation Sequencing have revealed that only 1.2% of the total human DNA codes for proteins, with the rest only being transcribed into regulatory RNA, known as non-coding RNA. Long non-coding RNAs (lncRNAs) are non-coding RNAs that have no or limited protein-coding potential and are >200nt in length. lncRNAs are key regulators of several cellular processes and have been associated with numerous vital organismal procedures, as well as with a variety of diseases, including cancer.  However, numerous lncRNAs are yet to be discovered, and of the thousands of annotated lncRNAs already, only a few have been functionally characterised.

Method

Our group has identified 40 lncRNAs that can potentially act as regulators of cell fate, via loss of function RNA interference studies using the Human Lincode NR lncRNA RefSeq v65 siRNA library.

Results

10 of the novel candidates belong to the class of long intergenic RNAs (lincRNAs) and their effects on short and long term survival were further tested on human embryonic kidney HEK293T cells using gene specific siRNAs and antisense LNA™ GapmeRs. Targeted silencing of six of the candidates led to increased short and long term survival, while for the rest four, the RNAi caused decreased cell survival, both short and long term.

Conclusion

These preliminary studies indicate that these candidate lncRNAs play crucial roles in deciding the cell fate of HEK293T cells and could be potential decision-maker molecules in other cells, including a variety of cancer cells, such as leukaemic and breast cancer cells.